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Genetic-Editing
Is this an evolutionary game changer?

Genetic Editing

The dangers that face the world can, every one of them, be traced back to science. The salvations that may save the world will, every one of them, be traced back to science.   — Isaac Asimov

Recent news reports about a scientific breakthrough in the ability to edit the genetic code of a human embryo have profoundly captured our interest. At the center of this technology is a process called CRISPR1. It is essentially a molecular “scalpel” which cuts out a faulty section of DNA from a chromosome pair thus allowing the chromosomes’ natural repair mechanisms to re-form a correct, undamaged sequence. This technology has now been used on single-celled human embryos, showing promise for permanently eradicating an inheritable genetic flaw in the developing embryo, according to the journal Nature, August 2, 2017. The implications of this research result are vast, and for many, controversial.

The Nature article showed how this gene repair technique could produce embryos without genetic defect, despite the eggs having been fertilized by sperm carrying a mutation that causes a severe form of inherited heart disease, hypertrophic cardiomyopathy. This disease has come to public and media attention due to its causation of the tragic, sudden, “death on the court” of many young, promising athletes.

A further implication of this technique, is that any embryo thus repaired, no longer carries the genetic mutation. It is gone, and any progeny of that repaired embryo cannot transmit the genetic defect. This raises the tempting scenario of complete elimination of a genetic disease from future generations.

There are both Pro’s and Con’s here however, and below we illustrate just some of them:

Pro’s:

The power of CRISPR, if refined and perfected, holds out the hope of reducing, or even ending, the propagation of certain genetic diseases, by way of modifying an affected embryo during in-vitro-fertilization (commonly known as IVF).

As an illustrative example, consider cystic fibrosis, a recessive genetic disease that affects all organ systems, but especially the lungs, leading to lifelong morbidity and foreshortened life. Even with current best care, cystic fibrosis leads to death generally in the late 30s-early 40s. If two parents are carriers of the gene, then statistically, 1 child of 4 will have the disease, 2 will be asymptomatic carriers whose progeny are at risk, and 1 will be “normal”-no disease and not a carrier. Without a technique for repair of the genetic defect, current IVF techniques would produce few “disease free” embryos for implantation: likely 1 out of 4. In theory, a technique like CRISPR could “fix” the 3 out of 4 embryos that would be affected by the presence of the diseased gene, thus leading to uniformly disease-free embryos for implantation. This would increase the odds of a successful implantation and possibly eliminate the need for, and cost of another IVF cycle. It also means that any “fixed” embryo could grow into a person who would be unable perpetuate the disease by transmission to their offspring.

It is tantalizing to imagine an even more sophisticated future for this technology when its success is no longer confined to single-celled embryos. It might ultimately be used like a genetic “antibiotic” on adults to “cure” genetic diseases.

Con’s:

A 2015 Pew Research poll revealed that 68% of US adults feel the use of embryonic gene editing makes them “very” or “somewhat” worried. In addition, the results of a 2013 Pew poll show slightly more than half the US population believes IVF itself is a moral issue. Many, especially those with religious convictions, strongly hold the position that IVF is not permissible given a respect for human life. They point to the embryos that are created, but not implanted or used, and feel that, given their belief that life begins at conception, the process is far too wasteful of human life. They also feel that techniques like IVF lead to a mentality in which human beings are treated as commodities to be bought, sold, altered, or ended. For these people, IVF and CRISPR are not moral options.

Assuming one does not reject the concept of IVF and embryo repair out of hand, the temptations and perils of being able to re-write the genetic code in nascent humans are already well-imagined and documented in countless works of science fiction. Now this ability may be within the reach of science in our lifetime. “Designer babies” or “enhanced humans” are within the grasp of technical possibility. Clearly, a worldwide framework of “rules” regarding this research – a framework that does not yet exist – would be essential in such a future. Perhaps it is fortunate that this kind of advanced gene editing is far more complex than that which has already been accomplished. We have some time to prepare before this potential technical offshoot of the current research becomes a reality.

The current headlines describing this new development in gene editing are suggestive of extremely near-term and far-ranging remedies. The enthusiasm is likely premature and would only apply to a very narrow slice of the population at present. In addition to moral and technical roadblocks, any kind of gene editing in the first few days of an embryo’s existence presupposes the use of IVF, which currently accounts for less than 2% of births in the US. It also assumes one or both IVF parents have had genetic testing to determine if they are carriers of a correctable disease (not guaranteed). Lastly, the cost and risk of the gene editing procedure would clearly need to outweigh that of simply identifying and removing all the disease carrying embryos from one or more IVF cycles and only using the naturally occurring “good” ones. That leaves a very small number of cases where embryonic gene editing would present itself as the logical (or only) course of action.

Given all the moral questions and potential for misuse, a management and/or governance framework that could successfully monitor and control how this technology is used would seem to be essential. The arrangement would have to be supported by all nations possessing the technology. It appears daunting since each will surely have different cultural norms surrounding the moral questions as well as differing legal systems. We think it can work though, helped by the fact that the very fearsome power of this technology will assist in ensuring its prudent use. A useful analogy is that of nuclear weapons (we know it sounds ridiculous, but bear with us). Shortly after their development, nuclear weapons were used by the United States in conflict putting an end to World War II. Nuclear weapons technology was demonstrated to be so powerful and devastating that other nations were simultaneously fearful of it and desirous of possessing it for themselves. In addition to the United States, eight more nations (for a total of nine) have now developed/acquired nuclear weapons in the last 72 years. As haphazard as the guardianship of these horrific weapons appears in the view of the media, there has been an effective framework in place for monitoring and controlling their use. The clear evidence of this fact is that there hasn’t been a single instance of nuclear weapon use in conflict in the 72 years since World War II. Respect for the power of the weapon and consequences of retaliation are so great, that even nations in a near constant state of war (e.g. Israel) have refrained from using them against other human beings. Ironically, this safety net is again being tested before our eyes in the current effort to prevent a terrorist nation (Iran) and a madman (Kim Jong Un of North Korea) from using these weapons.

So again, science and man’s relentless curiosity has handed us the prospect of a very sharp blade. Will it be a scalpel that can “heal with cold steel” or a sword that we use on our own kind? There is no undoing this discovery-we must find a humane way to harness it. But this scenario is not new. With each advance in technology, Man finds itself balancing anew on the knife’s edge.

1 CRISPR is an acronym standing for “Clustered Regularly Interspaced Short Palindromic Repeats”

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